The present invention is directed toward the use of minoxidil to support and to modulate the healing of wounds. Generally, the present invention is useful for the improvement or acceleration of the healing of wounds.
Minoxidil is a synthetic chemical with proven efficacy as a hypotensive agent and as a stimulant of hair growth. Thus it acts on different kinds of cells and induces different phenomena. These have useful sequelae in the treatment of hypertension and for enhancing hair growth.
The healing of wounds is a complex process. Certain reactions are initiated almost immediately after wounding including the clotting of blood and the aggregation of platelets. These steps are important as they stop the bleeding and they also initiate the first steps in the repair process. Cellular migrations are observed within the first day or two with the arrival of phagocytic cells such as neutrophils and macrophages. A day or two later, fibroblastic cells enter the wound and begin to produce the connective tissue components, including collagen, necessary for restoration of the dermal tissue. Endothelial cells also enter the wound and form the capillaries that restore the blood supply to the area.
Following the formation of the clot, epidermal cells at the margin of the wounds, as well as epithelial cells and organelles such as hair follicles, begin to migrate out from the edge of the wound and from the remnants of hair follicles in the wounded area. With minor wounds and in most other wound heating situations, these migrations of epithelial cells continue until the wounded area is completely covered by the epidermal cells. These cells are also known as keratinocytes.
Several studies have shown that the addition of exogenous factors to the wound accelerate wound healing. These wound stimulatory factors are polypeptides and can increase the formation of fibrous tissue. Also one such growth factor TGF.alpha., Schultz, et al., "Epithelial Wound Healing Enhances by Transforming Growth Factoralpha and Vaccinia Growth Factor", Science 235:350-2 (1987), has been reported to increase the epithelialization of experimental wounds. Clinically, wound healing is impaired or abnormal in a variety of conditions including diabetes, aging, following burns and in decubital conditions. The importance of the proper completion of each step in the wound healing process is illustrated in burns where epidermal coverage of the burn when delayed is associated with infection, fluid loss and abnormal scaring.
The sources of cells involved in the healing of skin include fibroblasts, smooth muscle cells and endothelial cells in the dermis and associated structures. Keratinocytes from the borders of the wound as well as epithelial cells from hair follicles are the major sources of the cells which restore the epidermis. In a small cut, the scar may be formed from fibroblasts, endothelial cells and epidermal cells which migrate in from the normal tissue around the wound. In a burn, smooth muscle cells may contribute the major portion of the dermis, while epithelial cells from hair follicles may provide much of the epidermal coverage over the tissue.